384 THE TYPHOID BACILLUS 



heated to 54-56 C. without losing any of its properties. It shows marked 

 agglutinating power (1 in 100,000, p. 413). In vitro it has no bactericidal 

 action, but in vivo it stimulates the leucocytes to take up and dissolve the 

 bacilli . It protects guinea-pigs and rabbits against the inoculation of lethal 

 doses of an exalted virus. It is markedly antitoxic (Balthazard and Chante- 

 messe), and neutralizes toxin in vitro. If given as a prophylactic, 2-24 hours 

 before the inoculation of the toxin, it will protect rabbits against the effects 

 of four times the lethal dose of toxin. When the serum is inoculated at 

 the same time as the toxin but at an independent site its action is less pro- 

 nounced, and animals which have received more than twice the lethal dose 

 succumb (Balthazard). When injected after the toxin the serum has still 

 less prophylactic and curative powers, and its efficacy varies inversely as the 

 time which has elapsed between the inoculation of the toxin and the 

 inoculation of the serum. The prophylactic properties of the serum 

 are short-lived and the immunity conferred lasts no longer than 10 or 

 12 days. 



3. Therapeutic application. Chantemesse's serum which in the laborator}^ 

 shows only feeble curative power has a marked influence on the phenomena 

 of opsonization, and it is probably to this that its undoubted therapeutic 

 properties in the treatment of enteric fever are due : according to statistics 

 published by Chantemesse the mortality in cases treated with the serum is 

 only 4 per cent. It is all important that the serum should be used in the 

 early stages of the disease. Originally Chantemesse inoculated repeated 

 doses of 5-15 c.c. sub-cutaneously, but the serum as now prepared is more 

 active and a single inoculation of a few drops is sufficient. 



B. Besredka's serum. An anti-endotoxic serum has been prepared by 

 Besredka, by inoculating killed cultures followed by living cultures of the 

 bacillus into the veins of animals. 



The serum neutralizes ten to twenty fatal doses of Besredka's endotoxin 

 and acts as a prophylactic to the inoculation of the endotoxin. 



Montefusco, who has used Besredka's serum in the treatment of enteric 

 fever at Naples, has obtained very satisfactory results, and thinks it will be 

 of great value in the treatment of the disease. 



7. Agglutination. Serum-diagnosis of enteric fever. 



Durham and Gruber were the first to show that [an antiserum] agglu- 

 tinates [its homologous organism]. This agglutinating property, which is a 

 reaction of infection (p. 225), is also manifested in the blood of persons 

 suffering from or who have recovered from an attack of enteric fever. 

 Agglutination can also be obtained with the blister fluid, milk, naturally 

 shed tears, and occasionally even with pus, urine, bile, etc. from these 

 persons. 



[A. S. Griinbaum first and] Widal [afterwards] utilized the agglutinat- 

 ing properties of the blood of enteric fever patients as a rapid and conclusive 

 method of diagnosis -the serum diagnosis of enteric fever. 



The power of agglutinating the typhoid bacillus is developed in the blood 

 of the patient as a rule in the early days of the illness, and while it may not 

 infrequently be delayed, it is only very exceptionally that it is absent through- 

 out the whole course of the disease ; (Widal and Sicard failed to get agglutina- 

 tion once only in 163 cases : Besson twice in 98 cases). The power of 

 agglutination may disappear during the early weeks of convalescence, and is 

 generally absent 6-8 months after recovery ; but occasionally it has been 

 present as long as 3 and even 7 years after the attack. 



A positive result obtained under the conditions to be immediately described 



